(1) Analysis of biologic products: a) Identification of "foreign" material in production samples (i.e. proteinaceous precipitate, salt crystals, fibers, and other materials have been found to be responsible in cases of rejected samples). b) Analysis of samples from bioassay test systems (i.e., examination of chimp liver biopsies for evidence of infection with Hepatitis C after animals were injected with biologics derived from blood). (2) Research: a) Studies on the effect of MHC genes in the regulation of retroviral production in mouse melanoma cells. Using immunoelectron microscopy we hav found that transfection of the MHC Class I H-2Kb, but not the Class II H- 2IAk gene results in the virtual elimination of two actively produced endogenous retroviruses, a budding ecotropic C-type particle and an intracellular intracisternal A-type particle (IAP). In H-2Kb-positive cells, the loss of IAP was due to a lack of IAP-specific mRNA while the los of C-type retroviral particles was associated with non-random alterations i proviral DNA. b) Studies on the role of defective interfering (DI) particles in causing CPE. Human macrophage-like cells (U937), exposed to a standard Sendai virus stock show abundant viral synthesis and a late CPE due to cell necrosis. In contrast, viral stocks containing DI particles show very little viral synthesis but nonetheless exhibit an early CPE consisting of widespread cellular disintegration by the mechanism of apoptosis (programme cell death). DI particles have not previously been shown to be capable of triggering apoptosis. (3) Research support: The EM Staff provides collaborative support for a wide variety of research projects initiated by CBER scientists.